An Exploratory Study of Suboxone (Buprenorphine/ Naloxone) Film Splitting: Cutting Methods, Content Uniformity, and Stability

Suboxone films are U.S. Food and Drug Administration approved to treat opioid dependence. While the package insert states that films should not be cut, physicians often prescribe film fractions for treatment and tapering. There is no data to support this practice, and this study was initiated to evaluate cutting methods, content uniformity, and stability of split films. Suboxone 8-mg buprenorphine/2-mg naloxone films were split using four methods: 1) ruler/razor cut, 2) scissor cut, 3) fold/rip, and 4) fold/scissor cut. United States Pharmacopeia Chapter \u3c905\u3e was used to evaluate the weight variation and content uniformity of split films. The stability of split films stored in polybags was evaluated over 7 days. A stability-indicating high-performance liquid chromatography method was used for content uniformity and stability evaluation. The weight variation results were acceptable for the half films from all four cutting methods, but this was not true for the quarter films. The method of ruler/razor cut was determined most favorable and used for the content uniformity test. Based on the high-performance liquid chromatography results, the half films from the ruler/razor cut method met the passing criteria of United States Pharmacopeia Chapter \u3c905\u3e with acceptance values of 9.8 to 10.4 for buprenorphine and 8.4 to 11.5 for naloxone (≤15 is considered passing). The stability results indicated that both actives retained \u3e97.7% of initial strength. Four cutting methods were found to be acceptable for splitting Suboxone films into half but not quarter fractions. The half films from the ruler/razor cut method also passed United States Pharmacopeia Chapter \u3c905\u3e content uniformity test. Both actives remained stable for 7 days when the half films were stored in polybags at room temperature

The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.

Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can also be linked to trypanothione reduction by an alternative pathway involving the thioredoxin-like protein tryparedoxin. The presence of this new pathway was first detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was identified as the intermediate molecule following purification, sequence analysis, antibody studies, and reconstitution of the redox cycle in vitro. The system can be readily saturated by trypanothione, the rate-limiting step being the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected parasites confers increased resistance to exogenous hydroperoxides. TcGPXI contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting signal for the glycosome, a kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, and biochemical fractionation, we have demonstrated that TcGPXI is localized to both the glycosome and the cytosol. The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites

Observation of coherent delocalized phonon-like modes in DNA under physiological conditions

Underdamped terahertz-frequency delocalized phonon-like modes have long been suggested to play a role in the biological function of DNA. Such phonon modes involve the collective motion of many atoms and are prerequisite to understanding the molecular nature of macroscopic conformational changes and related biochemical phenomena. Initial predictions were based on simple theoretical models of DNA. However, such models do not take into account strong interactions with the surrounding water, which is likely to cause phonon modes to be heavily damped and localized. Here we apply state-of-the-art femtosecond optical Kerr effect spectroscopy, which is currently the only technique capable of taking low-frequency (GHz to THz) vibrational spectra in solution. We are able to demonstrate that phonon modes involving the hydrogen bond network between the strands exist in DNA at physiologically relevant conditions. In addition, the dynamics of the solvating water molecules is slowed down by about a factor of 20 compared with the bulk

Comparing objective measures of environmental supports for pedestrian travel in adults

Background: Evidence is growing that the built environment has the potential to influence walking--both positively and negatively. However, uncertainty remains on the best approaches to representing the pedestrian environment in order to discern associations between walking and the environment. Research into the relationship between environment and walking is complex; challenges include choice of measures (objective and subjective), quality and availability of data, and methods for managing quantitative data through aggregation and weighting. In particular, little research has examined how to aggregate built environment data to best represent the neighborhood environments expected to influence residents' behavior. This study examined associations between walking and local pedestrian supports (as measured with an environmental audit), comparing the results of models using three different methods to aggregate and weight pedestrian features. Methods: Using data collected in 2005-2006 for a sample of 251 adult residents of Montgomery County, MD, we examined associations between pedestrian facilities and walking behaviors (pedestrian trips and average daily steps). Adjusted negative binomial and ordinary least-squares regression models were used to compare three different data aggregation techniques (raw averages, length weighting, distance weighting) for measures of pedestrian facilities that included presence, condition, width and connectivity of sidewalks, and presence of crossing aids and crosswalks. Results: Participants averaged 8.9 walk trips during the week; daily step counts averaged 7042. The three aggregation techniques revealed different associations between walk trips and the various pedestrian facilities. Crossing aids and good sidewalk conditions were associated with walk trips more than were other pedestrian facilities, while sidewalk facilities and features showed associations with steps not observed for crossing aids and crosswalks. Conclusion: Among three methods of aggregation examined, the method that accounted for distance from participant's home to the pedestrian facility (distance weighting) is promising; at the same time, it requires the most time and effort to calculate. This finding is consistent with the behavioral assumption that travelers may respond to environmental features closer to their residence more strongly than to more distant environmental qualities.close0

The genetic basis of adaptation to copper pollution in Drosophila melanogaster

Introduction: Heavy metal pollutants can have long lasting negative impacts on ecosystem health and can shape the evolution of species. The persistent and ubiquitous nature of heavy metal pollution provides an opportunity to characterize the genetic mechanisms that contribute to metal resistance in natural populations. Methods: We examined variation in resistance to copper, a common heavy metal contaminant, using wild collections of the model organism Drosophila melanogaster. Flies were collected from multiple sites that varied in copper contamination risk. We characterized phenotypic variation in copper resistance within and among populations using bulked segregant analysis to identify regions of the genome that contribute to copper resistance. Results and Discussion: Copper resistance varied among wild populations with a clear correspondence between resistance level and historical exposure to copper. We identified 288 SNPs distributed across the genome associated with copper resistance. Many SNPs had population-specific effects, but some had consistent effects on copper resistance in all populations. Significant SNPs map to several novel candidate genes involved in refolding disrupted proteins, energy production, and mitochondrial function. We also identified one SNP with consistent effects on copper resistance in all populations near CG11825, a gene involved in copper homeostasis and copper resistance. We compared the genetic signatures of copper resistance in the wild-derived populations to genetic control of copper resistance in the Drosophila Synthetic Population Resource (DSPR) and the Drosophila Genetic Reference Panel (DGRP), two copper-naïve laboratory populations. In addition to CG11825, which was identified as a candidate gene in the wild-derived populations and previously in the DSPR, there was modest overlap of copper-associated SNPs between the wild-derived populations and laboratory populations. Thirty-one SNPs associated with copper resistance in wild-derived populations fell within regions of the genome that were associated with copper resistance in the DSPR in a prior study. Collectively, our results demonstrate that the genetic control of copper resistance is highly polygenic, and that several loci can be clearly linked to genes involved in heavy metal toxicity response. The mixture of parallel and population-specific SNPs points to a complex interplay between genetic background and the selection regime that modifies the effects of genetic variation on copper resistance

A comparison of treatment outcomes for individuals with substance use disorder alone and individuals with probable dual diagnosis

The co-occurrence of substance use and mental health problems, often referred to as dual diagnosis (DD), is increasingly recognised as commonplace within substance abuse treatment programs. Two-hundred and thirty-four individuals from 9 Australian Salvation Army drug and alcohol rehabilitation programs completed a 3-month post-discharge telephone follow-up. Using a cut-off score from the Psychiatric Subscale of the Addiction Severity Index (5th ed.), 66.7% were classified as likely to have DD and 33.3% as substance use disorder only (SUD). Both groups reported comparable and decreased substance use levels at follow-up, yet DD individuals perceived less improvement in substance use problems. Comparable improvements were reported in the areas of: symptom distress and recovery from symptoms. This was despite greater scope for improvement in individuals with DD. Duration of treatment and access to post treatment services were also assessed. Understanding factors effecting treatment outcomes is imperative for the implementation of effective, evidence based treatment programs

Factors affecting mobile device use at festival attractions

To better comprehend mobile device acceptance and use at attractions and during tourism experiences broadly, we need to know and understand the factors that influence the decision to use technology in varying contexts. This presentation will discuss the Unified Theory of the Acceptance and Use of Technology 2 in relation to mobile device use at festivals. On-site interviews and survey data collection from 9 festivals reveals 5 new items that should be incorporated into this technology use model going forward. The implications will enable attraction staff and mobile device experience designers to ascertain appropriate ways to integrate mobile technology in the visitor’s experience

Pango lineage designation and assignment using SARS-CoV-2 spike gene nucleotide sequences

BACKGROUND: More than 2 million SARS-CoV-2 genome sequences have been generated and shared since the start of the COVID-19 pandemic and constitute a vital information source that informs outbreak control, disease surveillance, and public health policy. The Pango dynamic nomenclature is a popular system for classifying and naming genetically-distinct lineages of SARS-CoV-2, including variants of concern, and is based on the analysis of complete or near-complete virus genomes. However, for several reasons, nucleotide sequences may be generated that cover only the spike gene of SARS-CoV-2. It is therefore important to understand how much information about Pango lineage status is contained in spike-only nucleotide sequences. Here we explore how Pango lineages might be reliably designated and assigned to spike-only nucleotide sequences. We survey the genetic diversity of such sequences, and investigate the information they contain about Pango lineage status. RESULTS: Although many lineages, including the main variants of concern, can be identified clearly using spike-only sequences, some spike-only sequences are shared among tens or hundreds of Pango lineages. To facilitate the classification of SARS-CoV-2 lineages using subgenomic sequences we introduce the notion of designating such sequences to a “lineage set”, which represents the range of Pango lineages that are consistent with the observed mutations in a given spike sequence. CONCLUSIONS: We find that many lineages, including the main variants-of-concern, can be reliably identified by spike alone and we define lineage-sets to represent the lineage precision that can be achieved using spike-only nucleotide sequences. These data provide a foundation for the development of software tools that can assign newly-generated spike nucleotide sequences to Pango lineage sets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-08358-2

The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease